{"paper_id":"45c2768c-cdca-4d99-9dc2-db75e8171129","body_text":"Abstract\nHormones are present in oral fluids and undergo dynamic changes throughout life. Hormonal changes can influence the interactions between the microbial community and the host. The oral microbiome is sensitive to changes in the oral environment, and hormonal fluctuations can create conditions that favour the growth of certain types of bacteria over others. Since the gingival niche harbours the resident microbial community in the biofilm form, while saliva has a transient microbiota in the planktonic form, both could modulate the host–microbial interaction under hormonal oscillations.\nThe microbiome and hormones have a dynamic bidirectional interaction. Specific oral microorganisms can metabolize steroid hormones, disrupting their host regulation. Hormones can serve as host–microbial crosstalk related to health and disease. Hormonal imbalances are associated with systemic diseases such as polycystic ovary syndrome, endometriosis, cortisol-related conditions and oral cancer. Elucidating the complex relationship between steroid hormones and the oral microbiome offers valuable insights into the mechanisms of the disease and potential therapeutic avenues for maintaining oral and systemic health.\nAccess this chapter\nTax calculation will be finalised at checkout\nPurchases are for personal use only\nSimilar content being viewed by others\nAbbreviations\n- 11β-HSD2:\n-\n11β-hydroxysteroid dehydrogenase 2\n- ARs:\n-\nAndrogen receptors\n- CXCL1:\n-\nChemokine (C-X-C motif) ligand 1\n- DHT:\n-\n5 alpha-dihydrotestosterone\n- ERα:\n-\nOestrogen receptor alpha\n- ERβ:\n-\nOestrogen receptor beta\n- GCF:\n-\nGingival crevicular fluid\n- GRs:\n-\nGlucocorticoid receptors\n- GUS:\n-\nβ-glucuronidases\n- IL-1beta:\n-\nInterleukin-1 beta\n- OSCC:\n-\nOral squamous cell carcinoma\n- PCOS:\n-\nPolycystic ovary syndrome\n- TGF-beta1:\n-\nTransforming growth factor beta 1\nReferences\nAchu Joseph R, Ajitkumar S, Subbusamy Kanakasabapathy B, Santhanakrishnan M (2023) Evaluation of microbial profile in patients with polycystic ovary syndrome and periodontal disease: a case-control study. Int J fertil Steril [Internet] 17(4) [cited 2024 May 1]. https://doi.org/10.22074/ijfs.2023.550187.1272\nAdriaens LM, Alessandri R, Spörri S, Lang NP, Persson GR (2009) Does pregnancy have an impact on the subgingival microbiota? J Periodontol 80(1):72–81\nAgha-Hosseini F, Mirzaii-Dizgah I, Mansourian A, Khayamzadeh M (2009) Relationship of stimulated saliva 17β-estradiol and oral dryness feeling in menopause. Maturitas 62(2):197–199\nAkcalı A, Huck O, Buduneli N, Davideau JL, Köse T, Tenenbaum H (2014a) Exposure of Porphyromonas gingivalis to cortisol increases bacterial growth. Arch Oral Biol 59(1):30–34\nAkcalı A, Bostanci N, Özçaka Ö, Öztürk-Ceyhan B, Gümüş P, Buduneli N et al (2014b) Association between polycystic ovary syndrome, oral microbiota and systemic antibody responses. Abrams WR, editor. PLoS One 9(9):e108074\nAkyu (T)R, Tomihara K, Yamazaki M, Moniruzzaman R, Heshiki W, Sekido K et al (2021) Protumor role of estrogen receptor expression in oral squamous cell carcinoma cells. Oral Surg Oral Med Oral Pathol Oral Radiol 132(5):549–565\nAndrikopoulou M, Chatzistamou I, Gkilas H, Vilaras G, Sklavounou A (2013) Assessment of Angiogenic markers and female sex hormone receptors in pregnancy tumor of the gingiva. J Oral Maxillofac Surg 71(8):1376–1381\nArdila CM, Guzmán IC (2016) Association of P orphyromonas gingivalis with high levels of stress-induced hormone cortisol in chronic periodontitis patients. J Invest Clin Dent 7(4):361–367\nBecerik S, Özçaka Ö, Nalbantsoy A, Atilla G, Celec P, Behuliak M et al (2010) Effects of menstrual cycle on periodontal health and gingival crevicular fluid markers. J Periodontol 81(5):673–681\nCakmak O, Tasdemir Z, Aral CA, Dundar S, Koca HB (2016) Gingival crevicular fluid and saliva stress hormone levels in patients with chronic and aggressive periodontitis. J Clin Periodontol 43(12):1024–1031\nCarrillo-de-Albornoz A, Figuero E, Herrera D, Bascones-Martínez A (2010) Gingival changes during pregnancy: II. Influence of hormonal variations on the subgingival biofilm. J Clin Periodontol 37(3):230–240\nCelec P, Ostatníková D, Putz Z, Hodosy J, Burský P, Stárka L et al (2003) Circatrigintan cycle of salivary testosterone in human male. Biol Rhythm Res 34(3):305–315\nChaitra TR, Manuja N, Sinha AA, Kulkarni AU (2012) Hormonal effect on gingiva: pubertal gingivitis. Case Rep 2012(aug27 1):bcr2012006193\nChen C, Song X, Wei W, Zhong H, Dai J, Lan Z et al (2017) The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun 8(1):875\nChen P, Hong F, Yu X (2022) Prevalence of periodontal disease in pregnancy: a systematic review and meta-analysis. J Dent 125:104253\nCirillo N, Hassona Y, Pignatelli M, Gasparoto TH, Morgan DJ, Prime SS (2012) Characterization of a novel oral glucocorticoid system and its possible role in disease. J Dent Res 91(1):97–103\nClark DT, Soory M (2006) The metabolism of cholesterol and certain hormonal steroids by Treponema denticola. Steroids 71(5):352–363\nCoombes Z, Yadav V, McCoubrey L, Freire C, Basit A, Conlan R et al (2020) Progestogens are metabolized by the gut microbiota: implications for colonic drug delivery. Pharmaceutics 12(8):760\nCornejo Ulloa P, Van Der Veen MH, Brandt BW, Buijs MJ, Krom BP (2023) The effect of sex steroid hormones on the ecology of in vitro oral biofilms. Biofilms 6:100139\nCui J, Shen Y, Li R (2013) Estrogen synthesis and signaling pathways during aging: from periphery to brain. Trends Mol Med 19(3):197–209\nDemirel KJ, Guimaraes AN, Demirel I (2022) Effects of estradiol on the virulence traits of Porphyromonas gingivalis. Sci Rep 12(1):13881\nDoll C, Arsenic R, Lage H, Jöhrens K, Hartwig S, Nelson K et al (2015) Expression of estrogen receptors in OSCC in relation to histopathological grade. Anticancer Res 35(11):5867–5872\nDoll C, Bestendonk C, Kreutzer K, Neumann K, Pohrt A, Trzpis I et al (2021) Prognostic significance of estrogen receptor alpha in oral squamous cell carcinoma. Cancers 13(22):5763\nDou Y, Xin J, Zhou P, Tang J, Xie H, Fan W et al (2023) Bidirectional association between polycystic ovary syndrome and periodontal diseases. Front Endocrinol (Lausanne) 14:1008675\nDuran-Pinedo AE, Solbiati J, Frias-Lopez J (2018) The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome. NPJ Biofilms Microbiomes 4(1):25\nErvin SM, Li H, Lim L, Roberts LR, Liang X, Mani S et al (2019) Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem 294(49):18586–18599\nFteita D, Könönen E, Söderling E, Gürsoy UK (2014) Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria. Anaerobe 27:7–13\nFteita D, Könönen E, Gürsoy M, Söderling E, Gürsoy UK (2015) Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria? Anaerobe 36:14–18\nFujiwara N, Tsuruda K, Iwamoto Y, Kato F, Odaki T, Yamane N et al (2017) Significant increase of oral bacteria in the early pregnancy period in Japanese women. J Invest Clin Dent 8(1):e12189\nGandara BK, Leresche L, Mancl L (2007) Patterns of salivary estradiol and progesterone across the menstrual cycle. Ann N Y Acad Sci 1098(1):446–450\nGarbellotto GI, Reis FJ, Feoli AMP, Piovesan CH, Gustavo ADS, Oliveira MDS et al (2018) Salivary cortisol and metabolic syndrome component’s association. ABCD, Arq Bras Cir Dig [Internet] 31(1) 21 [cited 2024 May 1]. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-67202018000100312&lng=en&tlng=en\nGarcía-Gómez E, González-Pedrajo B, Camacho-Arroyo I (2013) Role of sex steroid hormones in bacterial-host interactions. Biomed Res Int 2013:1–10\nGenco RJ, LaMonte MJ, McSkimming DI, Buck MJ, Li L, Hovey KM et al (2019) The subgingival microbiome relationship to periodontal disease in older women. J Dent Res 98(9):975–984\nGolecka-Bakowska M, Mierzwinska-Nastalska E, Bychawska M (2010) Influence of hormone supplementation therapy on the incidence of denture stomatitis and on chemiluminescent activity of polymorphonuclear granulocytes in blood of menopausal-aged women. Eur J Med Res 15(S2):46\nGregory S, Denham SG, Lee P, Simpson JP, Homer NZM (2023) Using LC-MS/MS to determine salivary steroid reference intervals in a European older adult population. Meta 13(2):265\nGusberti FA, Mombelli A, Lang NP, Minder CE (1990) Changes in subgingival microbiota during puberty. A 4-year longitudinal study. J Clin Periodontol 17(10):685–692\nHu A, He J, Chu KH, Yu CP (2011) Genome sequence of the 17β-estradiol-utilizing bacterium sphingomonas strain KC8. J Bacteriol 193(16):4266–4267\nHu S, Ding Q, Zhang W, Kang M, Ma J, Zhao L (2023) Gut microbial beta-glucuronidase: a vital regulator in female estrogen metabolism. Gut Microbes 15(1):2236749\nIqbal J, Zaidi M (2009) Understanding Estrogen Action during Menopause. Endocrinology 150(8):3443–3445\nJang H, Patoine A, Wu TT, Castillo DA, Xiao J (2021) Oral microflora and pregnancy: a systematic review and meta-analysis. Sci Rep 11(1):16870\nJentsch HFR, März D, Krüger M (2013) The effects of stress hormones on growth of selected periodontitis related bacteria. Anaerobe 24:49–54\nJönsson D, Andersson G, Ekblad E, Liang M, Bratthall G, Nilsson BO (2004) Immunocytochemical demonstration of estrogen receptor β in human periodontal ligament cells. Arch Oral Biol 49(1):85–88\nKaan AMM, Kahharova D, Zaura E (2000) Acquisition and establishment of the oral microbiota. Periodontol 86(1):123–141\nKatz J, Onate MD, Pauley KM, Bhattacharyya I, Cha S (2011) Presence of Porphyromonas gingivalis in gingival squamous cell carcinoma. Int J Oral Sci 3(4):209–215\nKavoussi SK, West BT, Taylor GW, Lebovic DI (2009) Periodontal disease and endometriosis: analysis of the National Health and Nutrition Examination survey. Fertil Steril 91(2):335–342\nKonishi S, Brindle E, Guyton A, O’Connor KA (2012) Salivary concentration of progesterone and cortisol significantly differs across individuals after correcting for blood hormone values. Am J Phys Anthropol 149(2):231–241\nKumar PS (2000) Sex and the subgingival microbiome: do female sex steroids affect periodontal bacteria? Periodontol 61(1):103–124\nKumuda R, Suchetha K, Subhas GB, Urvashi AS, Harshini U (2018) Estimation of salivary cortisol level in post-menopausal women with psychosomatic disorders. Afr H Sci [Internet] 18(2) 22 [cited 2024 May 1]; Available from: https://www.ajol.info/index.php/ahs/article/view/173582\nLamont RJ, Koo H, Hajishengallis G (2018) The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol 16(12):745–759\nLeimola-Virtanen R, Salo T, Toikkanen S, Pulkkinen J, Syrjänen S (2000) Expression of estrogen receptor (ER) in oral mucosa and salivary glands. Maturitas 36(2):131–137\nLi X (Sunny), Li S, Kellermann G (2018) Simultaneous determination of three estrogens in human saliva without derivatization or liquid-liquid extraction for routine testing via miniaturized solid phase extraction with LC-MS/MS detection. Talanta 178:464–472\nLietzan AD, Simpson JB, Walton WG, Jariwala PB, Xu Y, Boynton MH et al (2023) Microbial β-glucuronidases drive human periodontal disease etiology. Sci Adv 9(18):eadg3390\nLin W, Jiang W, Hu X, Gao L, Ai D, Pan H et al (2018) Ecological shifts of Supragingival microbiota in association with pregnancy. Front Cell Infect Microbiol 8:24\nLy LK, Doden HL, Ridlon JM (2021) Gut feelings about bacterial steroid-17,20-desmolase. Mol Cell Endocrinol 525:111174\nMariotti A, Mawhinney M (2000) Endocrinology of sex steroid hormones and cell dynamics in the periodontium. Periodontology 61(1):69–88\nMarocchio LS, Giudice F, Corrêa L, Pinto Junior DDS, De Sousa SOM (2013) Oestrogens and androgen receptors in oral squamous cell carcinoma. Acta Odontol Scand 71(6):1513–1519\nMierzwińska-Nastalska E, Golecka-Bąkowska M, Bychawska M, Spiechowicz E (2013) Experimental immunology effect of hormone replacement therapy on the incidence and extent of Candida -associated denture stomatitis. CEJOI 2:226–230\nMin Q, Chen Y, Geng H, Gao Q, Zhang X, Xu M (2024) Causal relationship between PCOS and related sex hormones with oral inflammatory diseases: a bidirectional Mendelian randomization study. Front Endocrinol 14:1282056\nMirmonsef P, Hotton AL, Gilbert D, Burgad D, Landay A, Weber KM et al (2014) Free glycogen in vaginal fluids is associated with lactobacillus colonization and low vaginal pH. Fredricks DN, editor. PLoS One 9(7):e102467\nMutneja P, Dhawan P, Raina A, Sharma G (2012) Menopause and the oral cavity. Indian J Endocr Metab 16(4):548\nNagy KN, Sonkodi I, Szöke I, Nagy E, Newman HN (1998) The microflora associated with human oral carcinomas. Oral Oncol 34(4):304–308\nNarikiyo M, Tanabe C, Yamada Y, Igaki H, Tachimori Y, Kato H et al (2004) Frequent and preferential infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in esophageal cancers. Cancer Sci 95(7):569–574\nOjanotko-Harri A, Nikkari T, Harrl M, Paunio K (1990) Metabolism of progesterone and testosterone by Bacillus cereus strain Socransky 67 and Streptococcus mutans strain Ingbritt. Oral Microbiol Immunol 5(4):237–239\nOjanotko-Harri A, Laine M, Tenovuo J (1991) Metabolism of 17B-estradiol by oral Streptococcus mutans, streptococcus sanguis, Bacillus cereus and Candida albicans. Oral Microbiol Immunol 6(2):126–128\nOjanotko-Harri A, Forssell H, Laine M, Hurttia H, Bläuer M, Tuohimaa P (1992) Immunohistochemical detection of androgen receptors in human oral mucosa. Arch Oral Biol 37(6):511–514\nPan F, Zhang R, Wang G, Ding Y (2011) Oestrogen receptors are involved in the osteogenic differentiation of periodontal ligament stem cells. Biosci Rep 31(2):117–124\nParkar MH, Newman HN, Olsen I (1996) Polymerase chain reaction analysis of oestrogen and androgen receptor expression in human gingival and periodontal tissue. Arch Oral Biol 41(10):979–983\nPeters B, Santoro N, Kaplan R, Qi Q (2022) Spotlight on the gut microbiome in menopause: current insights. IJWH 14:1059–1072\nPlottel CS, Blaser MJ (2011) Microbiome and malignancy. Cell Host Microbe 10(4):324–335\nRoberts A, Matthews JB, Socransky SS, Freestone PPE, Williams PH, Chapple ILC (2002) Stress and the periodontal diseases: effects of catecholamines on the growth of periodontal bacteria in vitro. Oral Microbiol Immunol 17(5):296–303\nRoman-Torres CVG, Lourenço MEQ, Ferraz TS, Elias TDAB, Araújo MTMD, Pereira ACDJ et al (2023) Does the relationship between endometriosis and periodontal disease really exist? A systematic review. JAMMR 35(19):346–351\nSantana LCL, Spolidorio LC, Pitombo JCP, Basso FG, Guarenghi GG, Prates RC et al (2020) Testosterone increases fibroblast proliferation in vitro through androgen and estrogen receptor activation. J Int Acad Periodontol 22(3):146–155\nSaúco C, Rus MJ, Nieto MR, Barros C, Cantiga-Silva C, Lendines-Cordero D et al (2023) Hyposalivation but not Sjögren’s syndrome associated with microbial dysbiosis in women. Front Microbiol 14:1240891\nSchmidt BL, Kuczynski J, Bhattacharya A, Huey B, Corby PM, Queiroz ELS et al (2014) Changes in abundance of oral microbiota associated with oral cancer. PLoS One 9(6):e98741\nSimon JC, Marchesi JR, Mougel C, Selosse MA (2019) Host-microbiota interactions: from holobiont theory to analysis. Microbiome 7(1):5\nSobstyl A, Chałupnik A, Mertowska P, Grywalska E (2023) How do microorganisms influence the development of endometriosis? Participation of genital, intestinal and oral microbiota in metabolic regulation and immunopathogenesis of endometriosis. IJMS 24(13):10920\nSooriyamoorthy M, Gower DB (1989) Hormonal influences on gingival tissue: relationship to periodontal disease. J Clin Periodontol 16(4):201–208\nSoory M (1995) Bacterial steroidogenesis by periodontal pathogens and the effect of bacterial enzymes on steroid conversions by human gingival fibroblasts in culture. J Periodontal Res 30(2):124–131\nSuri R, Hellemann G, Cohen L, Aquino A, Altshuler L (2008) Saliva Estriol levels in women with and without prenatal antidepressant treatment. Biol Psychiatry 64(6):533–537\nTang X, Meng H, Han J, Zhang L, Hou J, Zhang F (2008) Up-regulation of estrogen receptor-β expression during osteogenic differentiation of human periodontal ligament cells. J Periodontal Res 43(3):311–321\nTatullo M, Nor J, Orrù G, Piattelli A, Cascardi E, Spagnuolo G (2024) Oral–gut–estrobolome axis may exert a selective impact on Oral cancer. J Dent Res 00220345241236125\nTeles F, Wang Y, Hajishengallis G, Hasturk H, Marchesan JT (2000) Impact of systemic factors in shaping the periodontal microbiome. Periodontology 85(1):126–160\nThomas V, Uppoor A, Pralhad S, Naik D, Kushtagi P (2018) Towards a common etiopathogenesis: periodontal disease and endometriosis. J Hum Reprod Sci 11(3):269\nTomasovic-Loncaric C, Fucic A, Andabak A, Andabak M, Ceppi M, Bruzzone M et al (2019) Androgen receptor as a biomarker of oral squamous cell carcinoma progression risk. Anticancer Res 39(8):4285–4289\nTramice A, Paris D, Manca A, Guevara Agudelo FA, Petrosino S, Siracusa L et al (2022) Analysis of the oral microbiome during hormonal cycle and its alterations in menopausal women: the “AMICA” project. Sci Rep 12(1):22086\nValimaa H, Savolainen S, Soukka T, Silvoniemi P, Makela S, Kujari H et al (2004) Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. J Endocrinol 180(1):55–62\nVittek J, Gordon GG, Rappaport SC, Munnangi PR, Southren AL (1982) Specific progesterone receptors in rabbit gingiva. J Periodontal Res 17(6):657–661\nWelling LLM, Jones BC, DeBruine LM, Conway CA, Law Smith MJ, Little AC et al (2007) Raised salivary testosterone in women is associated with increased attraction to masculine faces. Horm Behav 52(2):156–161\nWojcicki CJ, Harper DS, Robinson PJ (1987) Differences in periodontal disease-associated microorganisms of subgingival plaque in Prepubertal, pubertal and Postpubertal children. J Periodontol 58(4):219–223\nYang X, Guo Y, He J, Zhang F, Sun X, Yang S et al (2017) Estrogen and estrogen receptors in the modulation of gastrointestinal epithelial secretion. Oncotarget 8(57):97683–97692\nYang CY, Yeh YM, Yu HY, Chin CY, Hsu CW, Liu H et al (2018) Oral microbiota community dynamics associated with oral squamous cell carcinoma staging. Front Microbiol 9:862\nYeoh CC, Dabab N, Rigby E, Chhikara R, Akaev I, Gomez RS et al (2018) Androgen receptor in salivary gland carcinoma: a review of an old marker as a possible new target. J Oral Pathol Med 47(7):691–695\nZhang X, Li Y, Liu J, Liu X, Wang Z, Hu B (2006) Glucocorticoid receptor subunit gene expression in parotid gland and adenomas. Otolaryngol Head Neck Surg 135(6):849–852\nZhang B, Wu C, Chen W, Qiu L, Li S, Wang T et al (2020) The stress hormone norepinephrine promotes tumor progression through β2-adrenoreceptors in oral cancer. Arch Oral Biol 113:104712\nAcknowledgements\nThis work was supported by the Spanish Ministry of Science and Innovation Grant ID PID2020-118557GA-I00 funded by MICIU/AEI/10.13039/501100011033 (Aurea Simon-Soro) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 (Flávio Duarte Faria). Figure cartoons were created with BioRender.com.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEditor information\nEditors and Affiliations\nRights and permissions\nCopyright information\n© 2025 The Author(s), under exclusive license to Springer Nature Switzerland AG\nAbout this chapter\nCite this chapter\nRus, M.J., Sauco Carballo, C., Faria, F.D., Simon-Soro, A. (2025). Hormonal Environment Shapes the Oral Microbiome. In: Dame-Teixeira, N., Deng, D., Do, T. (eds) Oral Microbiome. Advances in Experimental Medicine and Biology, vol 1472. 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